Project Details
Projekt
HyperBone. Metabolic crosstalk between muscle, bone, and bone marrow adipocytes
Applicant
Professorin Hanna Taipaleenmäki, Ph.D.
Subject Area
Endocrinology, Diabetology, Metabolism
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 536691227
Skeletal muscles and bones are co-regulated by myokines and osteokines. In addition, evidence exists that muscles, bones and bone marrow adipocytes also interact at a metabolic level. For instance, immobilization or glucocorticoid-induced muscle atrophy is associated with a loss of bone mass and strength, whereas testosterone induces muscle hypertrophy and increases bone mass. In contrast, fat content in the bone marrow is often increased in conditions of muscle and bone loss and reduced in muscle hypertrophy. These clinical findings support the notion that a much less explored metabolic regulatory network between these tissues exists that could be implicated in metabolic diseases affecting the musculoskeletal system such as sarcopenia or osteoporosis. However, the metabolite exchange and flux within and between muscle, bone, and bone marrow adipocytes is thus far poorly understood. In the project, we propose to use advanced methods of metabolic research to investigate metabolic interactions between muscle, bone, and bone marrow fat. The central hypothesis of this project is that a metabolic crosstalk exists between muscle and bone and that the large bioenergetic need of the musculoskeletal system affects systemic metabolism. Using mouse and pig models of muscle hypertrophy and atrophy, co-culture systems, spatial metabolomics and flux analyses we aim to I) investigate the effect of muscle hypertrophy and atrophy on bone and bone marrow adipose tissue metabolism in a spatially resolved manner, II) determine how the large metabolite uptake required for global muscle hypertrophy and metabolite release during muscle atrophy affects the flux of metabolites in bone and bone marrow adipose tissue and III) identify regulatory mechanisms that influence the metabolic competition between muscle, bone, and bone marrow adipose tissue. We expect this project to reveal metabolic mechanisms underlying muscle-bone crosstalk as well as changes in the bone marrow adipose tissue in conditions of muscle hypertrophy and atrophy. The goal is to identify targets to stimulate muscle hypertrophy and consequently to treat metabolic bone diseases such as osteoporosis.
DFG Programme
Research Units
